2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.29 Nectin-4 Overexpression in ERBB2 Non-Small Cell Lung Cancer: A Multi-Center Study

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This study investigated the expression of nectin-4 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), focusing on those with ERBB2 mutations. Nectin-4 is a tumor-associated antigen overexpressed in certain lung cancer subtypes, and its expression was evaluated in correlation with ERBB2 mutations, known to affect therapeutic outcomes.<br /><br />The study included 21 patients, 14 with oncogenic ERBB2 mutations and 7 with wild-type ERBB2. The expression of nectin-4 was identified through immunohistochemistry and categorized based on H-score thresholds of 1, 15, and 50. Chi-squared analysis was conducted to compare nectin-4 positivity between ERBB2-mutated and wild-type samples.<br /><br />Results indicated that ERBB2-mutated NSCLC samples showed higher nectin-4 positivity rates compared to ERBB2-wild-type samples: 71.4% vs. 28.6% at H-score 1, 35.7% vs. 14.3% at H-score 15, and 21.4% vs. 14.3% at H-score 50. The differences were statistically significant at H-score thresholds 1 (p=0.00039) and 15 (p=0.02), but not at 50 (p=0.4456).<br /><br />The findings underscore that ERBB2-mutated NSCLC overexpresses nectin-4 compared to wild-type ones. Given the approval of enfortumab vedotin, an antibody-drug conjugate targeting nectin-4, for advanced urothelial carcinoma, the data suggest therapeutic potential for this drug in ERBB2-mutated NSCLC.<br /><br />Conclusively, the study advocates the standardization of positive expression thresholds in NSCLC and encourages the exploration of targeted therapies for NSCLC subtypes resistant to conventional treatments. This research advances the understanding of molecular characteristics of NSCLC, aiding in the development of personalized treatment approaches.

Asset Subtitle

Shilpa Mantri

Keywords

nectin-4

non-small cell lung cancer

NSCLC

ERBB2 mutations

immunohistochemistry

H-score

enfortumab vedotin

antibody-drug conjugate

targeted therapies

personalized treatment